Abstract
Objective:
Accumulating evidence has implicated insulin and the insulin-like growth factor (IGF) axis in colorectal carcinogenesis. Of interest, adiposity is likely to impose a greater risk on men than on women, which indicates that the association of insulin and the IGF axis with colorectal neoplasia may differ by gender. However, epidemiological evidence for this possible gender difference is limited to date.
Methods:
We measured plasma concentrations of C-peptide, IGF-I and IGF-binding proteins (IGFBPs) 1 and 3 in 1520 healthy volunteer examinees who underwent total colonoscopy between February 2004 and February 2005, and cross-sectionally investigated the association of these biomarkers with colorectal adenoma by gender. An unconditional logistic regression model was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for colorectal adenoma after adjustment for potential confounders.
Results:
We observed a positive association of C-peptide and IGF-I (Ptrend<0.001 and 0.02, respectively) and an inverse association of IGFBP-1 (Ptrend=0.002) with colorectal adenoma in men. Adjusted ORs of colorectal adenoma for the highest compared with the lowest quartile were also statistically significant for C-peptide (OR: 2.62, 95% CI: 1.71–4.01), IGF-I (OR: 1.63, 95% CI: 1.08–2.46) and IGFBP-1 (OR: 0.49, 95% CI: 0.32–0.75). In contrast, no measurable association was seen in women. Corresponding ORs for C-peptide, IGF-I and IGFBP-1 were 0.98 (95% CI: 0.56–1.71), 0.79 (95% CI: 0.44–1.43) and 1.05 (95% CI: 0.60–1.86), respectively. The gender difference was statistically significant for C-peptide (Pinteraction=0.03) and marginally significant for IGF-I and IGFBP-1 (Pinteraction=0.14 and 0.12, respectively).
Conclusion:
Our observations suggest that insulin and the IGF axis act differently by gender in colorectal carcinogenesis, at least in its early stage. The findings of this study further our understanding of the complexities of the gender difference in the association between adiposity and colorectal neoplasia.
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Acknowledgements
We are grateful to the participants of the Colorectal Adenoma Study in Tokyo, and to the doctors, nurses, administrative staff and researchers in the Research Center for Cancer Prevention and Screening who assisted with its conduct. This study was supported by the Ministry of Health, Labour and Welfare of Japan (Grant-in-Aid for the 3rd Term Comprehensive 10-Year-Strategy for Cancer Control and Grant-in-Aid for Cancer Research 17-9) and by the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Grant-in-Aid for Scientific Research on Priority Areas 17015049, Grant-in-Aid for Young Scientists A-19689014 and Grant-in-Aid for Young Scientists B-22790579). The study sponsors had no role in the design of the study; the collection, analysis and interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication.
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Yamaji, T., Iwasaki, M., Sasazuki, S. et al. Gender difference in the association of insulin and the insulin-like growth factor axis with colorectal neoplasia. Int J Obes 36, 440–447 (2012). https://doi.org/10.1038/ijo.2011.114
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DOI: https://doi.org/10.1038/ijo.2011.114
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